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Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: January 6, 2005
Last updated: September 27, 2013
Last verified: September 2013

This phase I trial is studying the side effects and best dose of lenalidomide in treating young patients with recurrent, progressive, or refractory CNS tumors. Lenalidomide may stop the growth of CNS tumors by blocking blood flow to the tumor. It may also stimulate the immune system in different ways and stop tumor cells from growing.

Condition Intervention Phase
Childhood Atypical Teratoid/Rhabdoid Tumor
Childhood Central Nervous System Germ Cell Tumor
Childhood Choroid Plexus Tumor
Childhood Craniopharyngioma
Childhood Ependymoblastoma
Childhood Grade I Meningioma
Childhood Grade II Meningioma
Childhood Grade III Meningioma
Childhood High-grade Cerebellar Astrocytoma
Childhood High-grade Cerebral Astrocytoma
Childhood Infratentorial Ependymoma
Childhood Low-grade Cerebellar Astrocytoma
Childhood Low-grade Cerebral Astrocytoma
Childhood Medulloepithelioma
Childhood Mixed Glioma
Childhood Oligodendroglioma
Childhood Supratentorial Ependymoma
Recurrent Childhood Brain Tumor
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Ependymoma
Recurrent Childhood Medulloblastoma
Recurrent Childhood Pineoblastoma
Recurrent Childhood Subependymal Giant Cell Astrocytoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Drug: lenalidomide
Procedure: perfusion-weighted magnetic resonance imaging
Procedure: diffusion-weighted magnetic resonance imaging
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of CC-5013 (Lenalidomide) in Pediatric Patients With Recurrent or Refractory Primary CNS Tumors

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD, estimated using the modified Continual Reassessment Method (CRM) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma drug concentrations and pharmacokinetic parameters, including volume of the central compartment (Vc/F), elimination rate constant (Ke), half-life (t1/2), apparent oral clearance (CL/F), and area under the plasma concentration time curve (AUC) [ Time Frame: Baseline and course 1 ] [ Designated as safety issue: No ]
    Presented in tabular and graphical form and determined using compartmental methods. Dose proportionality in pharmacokinetic parameters will be determined by performing one-way analysis of variance (ANOVA) on dose-normalized parameters.

Enrollment: 45
Study Start Date: November 2004
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lenalidomide)

Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-3 patients receive escalating doses of lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which an estimated 25% of patients experience dose-limiting toxicity.

Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Procedure: perfusion-weighted magnetic resonance imaging
Correlative studies
Other Name: PW-MRI
Procedure: diffusion-weighted magnetic resonance imaging
Correlative studies
Other Name: diffusion-weighted MRI
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


I. To estimate the MTD of oral CC-5013 administered to children with recurrent or refractory primary CNS tumors once daily for 21 days of a 28 day course.

II. To describe the toxicity profile and define the dose-limiting toxicity of CC-5013 in children with recurrent or refractory primary CNS tumors.


I. To characterize the pharmacokinetics of CC-5013 in children and adolescents. II. To characterize the pharmacogenetics of CC-5013 in children and adolescents.

III. To evaluate changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with CC-5013, and to investigate the correlation between changes in CECs and CEPs, plasma, serum and urine levels of proteins associated with angiogenesis including thrombospondin, b-FGF, TNF-α, IL-12, IL-8 and VEGF, and correlate these changes with changes in MR perfusion and clinical outcome.

IV. To evaluate changes in MR perfusion and diffusion during treatment.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-3 patients receive escalating doses of lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which an estimated 25% of patients experience dose-limiting toxicity.

All patients are followed for at least 30 days after the last dose of lenalidomide. Patients with treatment-related toxicity are followed for up to 3 months.


Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with a histological diagnosis of a primary CNS tumor (including histologically benign brain tumors (e.g. low-grade glioma) that is recurrent, progressive, or refractory to standard therapy; patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation of disease but should have clinical and/or radiographic evidence of progression
  • Karnofsky Performance Scale (KPS for >= 16 yrs of age) or Lansky Performance Score (LPS for ≤ 16 years of age) ≥ 60 assessed within two weeks prior to registration
  • Patient must be able to swallow capsules
  • Patients must have recovered from any significant acute toxicity associated with prior therapy; patients must have no known curative therapy available; patients will be eligible regardless of the number of prior therapies, as long as other eligibility criteria are met
  • Chemo: Prior use of thalidomide is acceptable; patients must have:

    • Received their last dose of known myelosuppressive anticancer chemotherapy or biological therapy at least three (3) weeks prior to study registration
    • Received their last dose of nitrosourea or mitomycin-C at least six (6) weeks prior to study registration
    • Received their last dose of other investigational agent or an anticancer drug known to not be myelosuppressive at least seven (7) days prior to study registration
  • XRT: Patients must have had their last fraction of craniospinal irradiation ≥ 3 months prior to registration and their last fraction of local irradiation to primary tumor ≥ 4 weeks prior to registration
  • Bone Marrow Transplant: ≥ 6 months since allogeneic bone marrow transplant and ≥ 3 months since autologous bone marrow/stem cell prior to registration
  • Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to registration (filgrastim, sargramostim, erythropoietin)
  • The following laboratory values must be assessed within two (2) weeks prior to registration and again within seven (7) days prior to the start of therapy; laboratory tests should be repeated within 48 hours of beginning therapy if there has been a significant clinical change
  • Absolute neutrophil count ≥ 1000/μl (unsupported)
  • Platelets ≥ 100,000/μl (unsupported)
  • Hemoglobin ≥ 8.0 g/dL (may be supported)
  • Serum creatinine within upper limit of institutional normal for age
  • Or GFR ≥ 70 ml/min/1.73m^2
  • Bilirubin ≤ 1.5 times upper limit of normal for age
  • SGPT (ALT) ≤ 2.5x institutional upper limit of normal for age
  • Albumin ≥ 2 g/dL
  • No overt renal, hepatic, cardiac or pulmonary disease
  • Female patients of childbearing potential must have negative serum or urine pregnancy test (sensitivity of at least 50mIU/ml); patients must not be pregnant or breast-feeding
  • All sexually active females must begin 2 methods of birth control, including 1 highly effective method, and 1 additional method (at the same time) at least 4 weeks prior to the first dose of CC-5013; this applies to all sexually active females of childbearing potential unless they have not had a menstrual period in 2 years or have undergone a hysterectomy
  • Patients of child fathering potential must agree to use latex condoms during intercourse with a woman while taking CC-5013 and for 4 weeks thereafter
  • Signed informed consent according to institutional guidelines must be obtained

Exclusion Criteria:

  • Patients with a body surface area (BSA) ≤ 0.4 m^2 are excluded
  • Patients with a first-degree relative with a history of venous thrombosis before age 50 yrs or an arterial thrombosis before age 40 yrs are excluded
  • Patients who have had a thromboembolic event that is not line-related are excluded
  • Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise a patient's ability to tolerate this therapy
  • Patients with any disease that would obscure toxicity or dangerously alter drug metabolism
  • Patients receiving any other chemotherapeutics or investigational agents
  • Patients with uncontrolled infection
  • Patients unable to swallow capsules
  • Patients with known hypersensitivity to anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00100880

United States, Tennessee
Pediatric Brain Tumor Consortium
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
Principal Investigator: Katherine Warren Pediatric Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00100880     History of Changes
Obsolete Identifiers: NCT00106990
Other Study ID Numbers: NCI-2012-03176, NCI-2012-03176, CDR653734, PBTC-018, PBTC-018, U01CA081457
Study First Received: January 6, 2005
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Optic Nerve Glioma
Central Nervous System Neoplasms
Cranial Nerve Diseases
Cranial Nerve Neoplasms
Eye Diseases
Meningeal Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Vascular Tissue
Nervous System Diseases
Nervous System Neoplasms
Optic Nerve Diseases
Optic Nerve Neoplasms
Peripheral Nervous System Neoplasms
Angiogenesis Inhibitors processed this record on February 27, 2015